2,4-BI-SUBSTITUTED AND 2,3,5-TRI-SUBSTITUTED PYRROLE DERIVATIVE AND INTERMEDIATE FOR PRODUCING THE SAME

摘要

PROBLEM TO BE SOLVED: To obtain the subject new compound useful as an anticancer drug having strong cytotoxicity. SOLUTION: This compound is expressed by the formula (R<1> is H or a protective group for an amino group; R<2> is H or a protective group for a carboxylic acid; R<3> is a lower alkyl; X is H or a halogen), e.g. 13-(tert-butoxycarbonyl)-2-(1- methylethyl)-13-azabicyclo[10.2.1]pentadeca-12(15), 14-diene-3,3-dicarboxylic dimethyl ester. The compound of the formula is obtained by reacting 3- formylpyrrole with a malonic acid derivative, reacting the resulting derivative with a lower alkylmagnesium halide, then, reacting the resulting product with Vilsmeier reagent to effect hydrolysis to form the corresponding derivative followed by protecting the amino group of the derivative, reacting the protected derivative with a ylide, deprotecting the triphenylmethyl group of the derivative obtained, followed by methanesulfonylation, and then iodination of the resulting product, and subjecting the iodinated product to a reaction with a base to form a macrocyclic pyrrole derivative, followed by catalytic hydrogenation of the double bond in the macrocyclic pyrrole derivative.